Psychotic Disorders in Later Life (Non-affective / non-organic) Dr Bob Barber December 2016

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1 Psychotic Disorders in Later Life (Non-affective / non-organic) Dr Bob Barber December 2016

2 Overview Diagnosis Treatment What have you learnt!

3 Which conditions?

4 Primary Psychotic Disorders Schizophrenia Schizoaffective Disorder Delusional Disorder Affective Disorder unipolar and bipolar Brief Psychotic Disorder Psychotic Disorder NOS

5 Secondary Psychotic Disorders commonest cause of paranoid symptoms Dementia with psychosis Delirium with psychosis Psychosis secondary to medical conditions Psychosis secondary to substance misuse or prescribed medication

6 Psychotic disorders across life span different pattern of illnesses

7 When assessing psychotic symptoms in late life. Always consider: Dementia Depression Physical illness Polypharmacy

8 Assessing psychotic symptoms in late life rough rule of thumb! Duration of symptoms relevant to diagnosis: Hours to days Weeks to months Months to years - delirium - depression - dementia - schizophrenia - delusional disorder

9 Psychotic symptoms in late life +/- cognitive impairment Without cognitive impairment systematised delusions auditory / multimodal hallucinations persistent With cognitive impairment fragmentary delusions visual hallucinations misidentification and misinterpretation

10 Psychosis in AD vs. Schizophrenia in Late life AD Schizophrenia (1) Incidence of illness AD common Less than 1% (2) Bizarre or complex Rare Frequent delusions (3) Misidentification Frequent Rare (4) Common type of Visual Auditory hallucinations (5) First rank symptoms Rare Common (6) Spontaneous remission (7) Need for long-term antipsychotics (8) Optimal antipsychotic dose More frequent Less frequent Less frequent More frequent 20% < Adult dose 50% < Adult dose (Jeste and Finkel, 2000).

11 Importance?

12 Importance of psychotic symptoms in late life Distress Associated with behavioural disturbances Impact on caregivers Increased risk of institutionalisation Greater mortality High cost to society

13 One of the most disenfranchised groups in health care is older people with psychotic disorders. The healthrelated well-being of older patients with psychosis living in the community is comparable to (or even slightly worse than) that of outpatients with AIDS (Patterson et al., 1996)

14 Late-onset Schizophrenia Background controversy Limitations of evidence++ Classification Prevalence Risk factors Symptoms Is there a meaningful differences between early & late onset Sz?

15 Late-onset Schizophrenia Classification Prevalence Risk factors Symptoms

16 Controversy re classification Is schizophrenia one illness or differences in early vs late onset?

17 Classification by ICD ICD-9 Late Paraphrenia: sub-coding of paranoid states : ICD-10 Removed Late Paraphrenia Schizophrenia (F20.0) Delusional Disorder (F22.0) Other persistent delusional disorder

18 Classification by DSM DSM III Sz had to begin before 45 years DSM III-R late-onset Sz : after 45 DSM IV no specific category for late-onset Sz DSM V Schizophrenia spectrum dimensional disorder. All subtypes of schizophrenia were deleted (paranoid, disorganized, catatonic, undifferentiated, and residual). Schizophrenia subtypes removed because of their limited diagnostic stability, low reliability, and poor validity, according to the APA

19 Howard & Rabins* International consensus group late onset Sz Schizophrenia: < 44 years Late onset schizophrenia: years Late life onset schizophrenia-like psychosis: > 60 years *BJP (1997) American JP (2000) 157(2):172-8 Rec reading Chapter 32 Oxford Textbook of Old Age Psychiatry

20 Late-onset Schizophrenia Classification Prevalence Risk factors Symptoms

21 Prevalence likely to increase Because wrt early onset Sz. The average life span of patients with onset before 60 is expected to increase: improved pharmacologic and other treatments general improvement in health and nutrition better long term survival Because wrt late onset Sz. Increased general life expectancy more people reaching at risk age for late onset Sz.

22 Epidemiology: 1 Some diagnostic criteria for schizophrenia exclude late-onset cases, and since many incidence and prevalence studies of psychotic disorders did not include patients older than 60 data for this group are scarce. The point prevalence of paranoid ideation in the general elderly population has been estimated to be 4% 6%, but most of these patients will have dementia. For individuals over 65 years of age, community prevalence estimates for schizophrenia range from 0.1% to 0.5%. Howard & Rabins 2000

23 Epidemiology: 2 (but data here is limited!) Incidence of Sz. peaks in early adult life & then a smaller peak in 7th & 8th decades, esp in women About 80% of older adults with schizophrenia have had an early onset of the disease and have a chronic course spanning several decades About 20% above age 45years, smaller subset - after age 60 Prevalence: 45 to 64 = 0.6% 65+ = 0.1% to 0.5% Incidence above age 44 = 12.6 per 100,000 Late-onset schizophrenia: 12% first presentations are over 64 year (Castle & Murray 1993)

24 Late-onset Schizophrenia Classification Prevalence Risk factors Symptoms

25 Brain Imaging - structural As seen in early-onset cases, CT and MRI reported nonspecific structural changes (e.g., higher ventricle-to-brain ratio and third ventricle volume) in patients with late-onset schizophrenia vs appropriate age-matched comparison subjects. Focal structural abnormalities such as volume reductions in left temporal lobe or superior temporal gyrus mirror changes reported in younger patients.

26 Brain imaging - functional Significance - tbc Regions of hypoperfusion in frontal and temporal areas, left posterior frontal and bilateral inferior temporal, and bilateral frontal and temporal lobes have been reported. Inconclusive - neuroreceptor studies that used positron emission tomography (PET) and single photon emission computed tomography (SPECT) have shown both an increase and no increase in D 2 receptor density in late-onset patients in relation to that of comparison subjects.

27 Neuroimaging abnormalities in L-O Sz. Present but significance uncertain: debate re normative changes with ageing / changes similar to other late-onset disorders Most consistent: Increased ventricular-brain ratio on CT (Naguib & Levy 1987) Enlarge ventricles (volumetric MRI) Inconclusive / limited data: Silent cerebral infarction Deep white matter hyperintensities

28 Risk factors - gender Later onset of schizophrenia among women and overrepresentation of women among late-onset cases are robust findings that are not readily explicable in terms of sex differences in care-seeking and societal role expectations or in delay between symptom emergence and service contact. It is conceivable that aging-associated psychosocial factors such as retirement, financial difficulties, bereavement, deaths of peers, or physical disability may contribute to the precipitation of the symptoms of schizophrenia in later life. The role of these factors has not, however, been studied systematically in late-onset patients. Howard & Rabins 2000

29 Theories to explain the later onset of schizophrenia in women include (a) There is a separate disorder genetically related to mood disorders, rather than schizophrenia (Castle & Murray, 1991), which explains why these patients show a better prognosis and response to treatment (Hogarty et al, 1974). (b) The condition is associated with a concurrent decline of oestrogen levels, and a relative excess of dopamine D2 receptors (Pearlson & Rabins, 1988; Seeman & Lang, 1990). (c) Psychosocial factors, such as better use of coping behaviour strategies and social support schemes, delay the onset of schizophrenic symptoms among women (Riecher et al, 1990).

30 Risk factors - genetics Most of the reported family studies that involved patients with lateonset schizophrenia suffer from methodological shortcomings Good evidence: relatives of very-late-onset patients < morbid risk for schizophrenia than the relatives of early-onset schizophrenia patients. Premorbid educational, occupational, and psychosocial functioning is less impaired in late-onset than early-onset schizophrenia, although many late-onset patients are reported to have had premorbid schizoid or paranoid personality traits that fell short of currently accepted diagnostic criteria for personality disorders Howard & Rabins 2000

31 Risk factors - Hearing loss and Late-Onset Sz? Increased rate of hearing impairment noted in patients with late paraphrenia (Cooper et al 1976) 40% moderate to severe hearing impairment often profound, longstanding, bilateral & conductive (than degenerative) could it be related to auditory hallucinations / pre-existing tendency to social isolation / or less likely to seek treatment for hearing problems so more evident or service less well geared to met the needs of patients with co-morbid problems?? However, most hearing impaired elderly do not develop psychopathology More likely to have depression than psychosis

32 Schizophrenia in late life - a distinct entity? The Case for Heterogeneity With Increased Onset Age Schizophrenia-like psychoses can arise at any time in the life cycle between childhood and old age. The expression of such psychotic symptoms shows greatest variation when onset age is at both extremes of life. Since the aetiologies and the distinctive pathophysiologies of schizophrenia are at present unknown, variations in epidemiology, symptomatology, pathophysiology, and treatment response with age at onset may point to this hetereogeneity Howard & Rabins 2000

33 Late-onset Schizophrenia Classification Prevalence Risk factors Symptoms

34 Patients with late vs early onset Sz are: More likely.* Visual, tactile and olfactory hallucinations Partition delusions & persecutory delusions common may also have delusions re Reference, Misidentification, Control, Hypochondriasis, Grandiosity, Religion Auditory hallucinations Less likely. Formal thought disorder Negative symptoms - affective flattening or blunting/ poverty speech Catatonic symptoms Thought insertion and withdrawal *Howard et al Br J Psychiatry Sep;163: A comparative study of 470 cases of early-onset and lateonset schizophrenia.

35 Delusions and hallucinations usually dominate the clinical picture. Kay & Roth (1961) offered a vivid description: Neighbours, landlords, or relatives are implicated in plots to be rid of the patients, or to annoy or interfere with them through jealousy or simply for amusement Patients feel drugged, hypnotised, have their thoughts read, their minds or bodies worked upon by rays, machines or electricity, complain that they are spied upon, can get no privacy in thought or act (auditory hallucinations) consist of threatening, accusing, commanding or cajoling voices, jeering commentaries, screams, shouts for help, obscene words and songs, music, loud bangs, rappings, shots or explosions their thoughts are repeated aloud God, spirits, distant or deceased relatives, or most often, jealous, hostile neighbours are held responsible (for these phenomena).

36 Neuropsychological Impairments Early-onset schizophrenia: studies of patients who have grown old have reported both deterioration, stability or improvement. Although a precise characterization of the cognitive abnormality that accompanies schizophrenia is still awaited, young patients seem to be impaired on most cognitive tasks. Late-onset schizophrenia: patients (like earlier-onset patients) perform significantly less well than comparison subjects on measures of executive functions, learning, motor skills, and verbal ability, Howard & Rabins 2000

37 The patient with L-O Sz. Socially isolated female Unmarried or widowed many years Few or no children Independent and resistive of assistance perceived as intrusion personality style: suspicious, sensitive, quarrelsome source rather than result of social isolation/low marriage rate? Quietly psychotic for months to years Present because of self-neglect or social nuisance Some cognitive decline but not clinically dementing

38 Other findings in Late-Onset Sz.

39 Table as summary of differences Onset Gender Schizophrenia early to middle adult life Schizophrenia late adult life nearly 25% have late-onset schizophrenia (with onset of illness usually in middle age), while the remaining 75% have had schizophrenia since adolescence or early adulthood. > Female (?? Role of oestrogens) Symptoms Less negative symptoms (blunting / withdrawal) and thought More visual hallucinations No difference in type of cognitive deficits has been found between early- versus late-onset cases. Later onset of schizophrenia is, however, associated with somewhat milder cognitive deficits, especially in the areas of learning and abstraction/cognitive flexibility. Family history Greater family history No evidence late onset Sz. ass with increased familial aggregation of Alzheimer s disease, vascular dementia, dementia with Lewy bodies, or apolipoprotein E genotype.

40 Schizophrenia early to middle adult life Schizophrenia late adult life Brain imaging Course Treatment No differences both share nonspecific brain-imaging abnormalities such as mild ventricular enlargement and white matter hyperintensities, May be more remitting need for and tolerance to lower doses (10-25% dose used in younger adults) of antipsychotic medications. Mortality Co-morbidities higher mortality from suicide and other causes (Jeste et al., 1997) Few controlled trials of the use of typical antipsychotic medications in these patients have been reported. In open studies, 48% 61% of patients show full remission of psychotic symptoms with treatment, although poor compliance may render treatment in the community less successful Increase adding complexity. Age associated frailty. Pharmacotherapy in older patients is complicated by changes in pharmacokinetics and pharmacodynamics. The risk of adverse effects is considerably higher in the elderly.

41 Treatment issues?

42 Response to Treatment Few controlled trials of the use of typical antipsychotic medications in these patients have been reported. In open studies, 48% 61% of patients show full remission of psychotic symptoms with treatment, although poor compliance may render treatment in the community less successful. Psychosocial and behavioral approaches, which include cognitive behavior therapy and social skills training, are important adjuncts to pharmacological therapy for patients with schizophrenia, although their role in the management of patients with late-onset schizophrenia remains to be investigated. Howard & Rabins 2000

43 Treatment issues in Late-Onset Sz When to treat? distress /agitation/ aggression/ social nuisance Therapeutic alliance often difficult to establish Treatment modalities: medication / environmental change/ psychosocial support Total resolution of symptoms often not achieved: encapsulation of delusional system reduced acting out

44 Medication issues in Late-Onset Sz Sensitivity to neuroleptics: low dose: risperidone mg/day (Howard 1998) olanzapine mg/day depot (? smaller doses - eg 15mg depixol every 2 weeks - & better compliance) Interaction with physical problems / medication Parkinson s Disease / Cardiovascular / Cerebrovacular Vulnerability to Tardive Dyskinesia elderly / female / cognitive impairment Reducing tolerance over time

45 Treatment issues: Graduates Often not monitored and reviewed over the long term Sequelae of chronic mental illness: Self-neglect/physical illness Substance abuse (alcohol, tobacco) Social isolation Multidisciplinary management: Medication needs General health needs Accommodation needs Family support needs

46 Medication issues: Graduates Regular medication review: increasing physical frailty positive symptoms tend to attenuate negative symptoms tend to worsen risk of tardive dyskinesia increases Medication options: dose reduction change to atypical agent depot to oral Changing to atypical neuroleptic: gradual process to minimise exacerbation of TD withdrawal dyskinesia gradually settles

47 Learning points? Importance of psychosis Clinical presentation variation with age Differential diagnosis organic vs functional Management? engagement low dose antipsychotic

48 Further reading / appendix Late-Onset Schizophrenia and Very-Late-Onset Schizophrenia-Like Psychosis: An International Consensus Robert Howard; Peter V. Rabins, M.P.H.,; Mary V. Seeman; Dilip V. Jeste; the International Late-Onset, Schizophrenia Group Am J Psychiatry 2000;157: Howard & Rabins BJP (1997) Rec reading Chapter 32 Oxford Textbook of Old Age Psychiatry *BJP (1997) American JP (2000) 157(2):172-8 Chapter 32 Oxford Textbook of Old Age Psychiatry

49 Classification of Paranoid disorders of Late Life Kraepelin (1894) dementia praecox: disorder of emotion & will Paraphrenia: hallucinations & delusions with no deterioration in affect, will & personality Paranoia: delusional system Kraepelin (1913) doubts in own mind about validity of parapherenia & also never saw late onset as aspect of paraphrenia E Bleuler (1911) schizophrenia(s) M Bleuler (1943) 126 patients 15% developed illness age > 40years

50 Late Paraphrenia Roth s criteria (Roth & Morrisey, 1950s) > years Predominance of females Systematised delusions +/- hallucinations Paranoid or schizoid personality Absence of personality deterioration Absence of dementia or affective disturbance

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